Abstract
Animal studies of nutritional programming confirm the biological principle underpinning the “Barker Hypothesis”. Most studies have modelled the hypothesis in its simplest form, seeking to test the proposal that low birthweight predicts hypertension and, indeed, growth restricted offspring in many species do exhibit raised blood pressure as adults. A growing body of work with rodents has considered the programming effects of restricting single nutrients, including low protein feeding, high fat feeding and micronutrient restriction. Quite subtle shifts in the composition of the diet in pregnancy appear to produce potent effects, with hypertension, glucose intolerance, impaired immunity and reduced longevity noted with restriction of maternal protein, iron, sodium or calcium intakes. Although the nature and severity of the insults applied vary greatly between models, the general finding is that either balanced undernutrition or restriction of specific nutrients promotes metabolic and physiological disturbance and also relative adiposity in adult life. Intrauterine influences upon feeding, metabolism and the deposition of adipose tissue may well be mediated at the level of the hypothalamus. Microarray studies of the offspring of protein-restricted pregnant rats, which exhibit a preference for a high-fat food, indicate altered hypothalamic expression of a number of genes relating to signal transduction and homeostatic functions. The common outcomes of a range of nutrient manipulations in pregnancy suggest that a small number of common mechanisms may operate to reset the structure and long-term functions of most tissues. Timing and duration of the insult appears to be a more important determinant of long-term disease outcomes than the nature of the nutrient challenge.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Huxley R, Neil A, Collins R. Unravelling the fetal origins hypothesis: Is there really an inverse association between birth weight and subsequent blood pressure? Lancet 2002; 360:659–665.
Kramer MS, Joseph KS. Enigma of fetal/infant-origins hypothesis. Lancet 1996; 348:1254–1255.
Lucas A, Fewtrell MS, Cole TJ. Fetal origins of adult disease-the hypothesis revisited. BMJ 1999; 319:245–9.
Langley-Evans SC. Fetal programming of cardiovascular function through exposure to maternal undernutrition. Proc Nutr Soc 2001; 60:505–513.
Hoet JJ, Hanson MA. Intrauterine nutrition: Its importance during critical periods for cardiovascular and endocrine development. J Physiol 1999; 514:617–27.
Persson E, Jansson T. Low birth weight is associated with elevated adult blood pressure in the chronically catheterized guinea-pig. Acta Physiol Scand 1992; 115:195–196.
Jansson T, Lambert GW. Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3–4 months of age. J Hypertens 1999; 17:1239–48.
Woodall SM, Johnston BM, Breier BH et al. Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Ped Res 1996; 40:438–443.
Vickers MH, Breier BH, Cutfield WS et al. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab 2000; 279:E83–7.
Woodall SM, Breier BH, Johnston BM et al. A model of intrauterine growth retardation caused by chronic maternal undernutrition in the rat: Effects on the somatotrophic axis and postnatal growth. J Endocrinol 1996; 150:231–42.
Bertram CE, Hanson MA. Animal models and programming of the metabolic syndrome. Br Med Bull 2001; 60:103–121.
Fall CHD, Vijayakumar M, Barker DJP et al. Weight in infancy and prevalence of coronary heart disease in adult life. BMJ 1995; 310:17–19.
Curhan GC, Chertow GM, Willett WC et al. Birth weight and adult hypertension and obesity in women. Circulation 1996; 94:1310–1315.
Moore VM, Miller AG, Boulton TJC et al. Placental weight, birth measurements and blood pressure at age 8 years. Arch Dis Child 1996; 74:538–541.
Forsen T, Eriksson JG, Tuomilehto J et al. Growth in utero and during childhood among women who develop coronary heart disease: Longitudinal study. BMJ 1999; 319:1403–1407.
Langley-Evans SC. Nutritional programming and the development of hypertension. In: McCarty R, Blizzard DA, Chevalier RL, eds. Development of the Hypertensive Phenotype: Basic and Clinical Studies. Handbook of Hypertension. Vol. 19. Amsterdam: Elsevier, 1999:539–574.
Edwards CRW, Benediktsson R, Lindsay RS et al. Dysfunction of placental glucocorticoid barrier: Link between fetal environmental and adult hypertension. Lancet 1993; 341:355–357.
Langley-Evans SC. Intrauterine programming of hypertension by glucocorticoids. Life Sci 1997; 60:1213–1221.
Langley-Evans SC, Phillips GJ, Benediktsson R et al. Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension. Placenta 1996; 17:169–172.
Gardner DS, Jackson AA, Langley-Evans SC. Maintenance of maternal diet-induced hypertension in the rat is dependent upon glucocorticoids. Hypertension 1997; 30:1525–1530.
Young LE. Imprinting of genes and the Barker hypothesis. Twin Research 2001; 4:307–17.
Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 2002; 16:6–21.
Petrie L, Duthie SJ, Rees WD et al. Serum concentration sof homocystein are elevated during early pregnancy in rodent models of fetal programming. Br J Nutr 2002; 88:471–77.
Langley-Evans SC, Welham SJM, Jackson AA. Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci 1999; 64:965–974.
Snoeck A, Remacle C, Reussens B et al. Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biol Neonate 1990; 57:107–118.
Bayol S, Jones D, Goldspink G et al. Influence of maternal nutrition on postnatal skeletal muscle growth. Arch Animal Breeding 2003; 46:158–159.
Sahajpal V, Ashton N. Renal function and AT1 receptor expression in young rats following intrauterine exposure to a maternal low protein diet. Clin Sci 2003; 104:607–614.
McMullen S, Gardner DS, Langley-Evans SC. Prenatal programming of angiotensin II type 2 receptor expression in the rat. Br J Nutr 2004; 91:133–140.
Vehaskari VM, Aviles DH, Manning J. Prenatal programming of adult hypertension in the rat. Kid Int 2001; 59:238–245.
Zimanyi MA, Bertram JF, Black JM. Nephron number in the offspring of rats fed a low protein diet during pregnancy. Image Anal Stereol 2000; 19:219–222.
Plagemann A, Harder T, Rake A et al. Hypothalamic nuclei are malformed in weanling offspring of low protein malnourished rat dams. J Nutr 2000; 130:2582–2590.
Holemans K, Gerber R, Meurrens K et al. Maternal food restriction in the second half of pregnancy affects vascular function but not blood pressure of rat female offspring. Br J Nutr 1999; 81:73–79.
Ozaki T, Nishina H, Hanson MA et al. Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. J Physiol 2001; 530:141–152.
Kind KL, Simonetta G, Clifton PM et al. Effect of maternal feed restriction on blood pressure in the adult guinea pig. Exp Physiol 2002; 87:469–477.
Langley-Evans SC, Langley-Evans AJ, Marchand MC. Nutritional programming of blood pressure and renal morphology. Arch Physiol Biochem 2003; 111:8–16.
Langley-Evans SC, Gardner DS, Jackson AA. Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. J Reprod Fert 1996; 106:307–312.
Langley SC, Jackson AA. Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diet. Clin Sci 1994; 86:217–222.
Langley-Evans SC, Gardner DS, Jackson AA. Evidence of programming of the hypothalamic-pituitary-adrenal axis by maternal protein restriction during pregnancy. J Nutr 1996; 126:1578–1585.
Langley-Evans SC, Phillips GJ, Jackson AA. In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr 1994; 13:319–324.
Langley-Evans SC, Jackson AA. Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets. Comp Biochem Physiol 1995; 110A:223–228.
Langley-Evans SC, Welham SJM, Sherman RC et al. Weanling rats exposed to maternal low protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clin Sci 1996; 91:607–615.
Kwong WY, Wild AE, Roberts P et al. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 2002; 127:4195–4202.
Mackenzie HS, Lawler EV, Brenner BM. Congenital oligonephropathy: The fetal flaw in essential hypertension? Kid Int 1996; 49(suppl 55):S30–S34.
Marchand MC, Langley-Evans SC. Intrauterine programming of nephron number: The fetal flaw revisited. J Nephrology 2001; 14:327–331.
Ray PE, Bruggeman LA, Horikoshi S et al. Angiotensin II stimulates human fetal mesangial cell proliferation and fibronectin biosynthesis by binding to AT1 receptors. Kid Int 1994; 45:177–184.
Siragy HM. Angiotensin receptor blockers: How important is selectivity? AJH 2002; 15:1006–1014.
Rees WD, Hay SM, Buchan V et al. The effects of maternal protein restriction on the growth of the rat fetus and its amino acid supply. Br J Nutr 1999; 81:243–250.
Jackson AA, Dunn RL, Marchand MC et al. Increased systolic blood pressure in rats induced by maternal low protein diet is reversed by dietary supplementation with glycine. Clin Sci 2002; 103:633–639.
Rees WD. Manipulating the sulfur amino acid content of the early diet and its implications for long-term health. Proc Nutr Soc 2002; 61:71–7.
Dunn RL, Burdge GC, Jackson AA. Folic acid reduces blood pressure in rat offspring from maternal low protein diet but increases blood pressure in offspring of the maternal control diet. Ped Res 2003; 53:2A.
Dance CS, Brawley L, Dunn RL et al. Folate supplementation of a protein restricted diet during pregnancy: Restoration of vascular dysfunction in small mesenteric arteries of female adult rat offspring. Ped Res 2003; 53:19A.
Langley-Evans SC. Intrauterine programming of hypertension: Nutrient interactions. Comp Biochem Physiol 1996; 114A:327–333.
Crowe C, Dandekar P, Fox M et al. The effects of anaemia on heart, placenta and body weight, and blood pressure in fetal and neonatal rats. J Physiol (London) 1995; 488:515–519.
Gambling L, Dunford S, Wallace DI et al. Iron deficiency during pregnancy affects postnatal blood pressure in the rat. J Physiol 2003; 552:603–10.
Battista M-C, Oligny LL, St-Louis J et al. Intrauterine growth restriction in rats is associated with hypertension and renal dysfunction in adulthood. Am J Physiol 2002; 283:E124–E131.
Bergel E, Belizan JM. A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats. Br J Obstet Gynaecol 2002; 109:540–545.
Holemans K, Gerber R, O’Brien-Coker I et al. Raised saturated-fat intake worsens vascular function in virgin and pregnant offspring of streptozocin-diabetic rats. Br J Nutr 2000; 84:285–296.
Khan IY, Taylor PD, Dekou V et al. Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension 2003; 41:168–75.
Woods LL, Ingelfinger JR, Nyengaard JR et al. Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res 2001; 49:460–7.
Tonkiss J, Trzcinska M, Galler JR et al. Prenatal malnutrition-induced changes in blood pressure-Dissociation of stress and nonstress responses using radiotelemetry. Hypertension 1998; 32:108–114.
Ozanne SE, Martensz ND, Petry CJ et al. Maternal low protein diet in rats programmes fatty acid desaturase activities in the offspring. Diabetologia 1998; 41:1337–42.
Merlet-Benichou C, Gilbert T, Muffat-Joly M et al. Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatr Nephrol 1994; 8:175–180.
Sparre T, Reusens B, Cherif H et al. Intrauterine programming of fetal islet gene expression in rats—effects of maternal protein restriction during gestation revealed by proteome analysis. Diabetologia 2003; 46:1497–511.
Langley-Evans SC. Critical differences between two low protein diet protocols in the programming of hypertension in the rat. Int J Food Sci Nutr 2000; 51:11–17.
Anguita RM, Sigulem DM, Sawaya AL. Intrauterine food restriction is associated with obesity in young rats. J Nutr 1993; 123:1421–1428.
Jones AP, Friedman MI. Obesity and adipocyte abnormalities in offspring of rats undernourished during pregnancy. Science 1982; 215:1518–1519.
Jones AP, Simson EL, Friedman MI. Gestational undernutrition and the development of obesity in rats. J Nutr 1983; 114:1482–1484.
Bellinger L, Lilley C, Langley-Evans SC. Prenatal exposure to a low protein diet programmes a preference for high fat foods in the rat. Ped Res 2003; 53:P603.
Daenzer M, Ortmann S, Klaus S et al. Prenatal high protein exposure decreases energy expenditure and increases adiposity in young rats. J Nutr 2002; 132:142–144.
McDade TW, Kuzawa CW, Adair LS et al. Prenatal and early postnatal environments are significant predictors of total immunoglobulin E concentration in Filipino adolescents. Clin Exp Allergy 2004; 34:44–50.
Benn CS, Jeppesen DL, Hasselbalch H et al. Thymus size and head circumference at birth and the development of allergic diseases. Clin Exp Allergy 2001; 31:1862–6.
Moore SE, Cole TJ, Collinson AC et al. Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa. Int J Epidemiol 1999; 28:1088–95.
Langley-Evans SC, Buttery PJ, Wakelin D. Fetal exposure to a maternal low protein diet and the immune system. Proc Nutr Soc 2002; 61:121A.
Beach RS, Gershwin ME, Hurley LS. Gestational zinc deprivation in mice: Persistence of immunodeficiency for three generations. Science 1982; 218:469–471.
Langley SC, Seakins M, Grimble RF et al. The acute phase response of adult rats is altered by in utero exposure to maternal low protein diets. J Nutr 1994; 124:1588–1596.
Tappia PS, McCarthy HD, Langley-Evans SC et al. Prenatal nutritional adequacy and gender influence the ability of adult rats to produce interleukins 1, 6 and tumour necrosis alpha. Proc Nut Soc 1994; 53:182A.
Calder PC, Yaqoob P. The level of protein and type of fat in the diet of pregnant rats both affect lymphocyte function in the offspring. Nut Res 2000; 20:995–1005.
Langley-Evans SC, Wakelin D, Buttery PJ. Undernutrition during fetal life programmes immune function in the rat. Ped Res 2003; 53:P104.
Jennings BJ, Ozanne SE, Dorling MW et al. Early growth determines longevity in male rats and may be related to telomere shortening in the kidney. FEBS Lett 1999; 448:4–8.
Sayer AA, Dunn RL, Langley-Evans SC et al. Intrauterine exposure to a maternal low protein diet shortens lifespan in rats. Gerontology 2001; 47:9–14.
Ozanne SE, Hales CN. Lifespan: Catch-up growth and obesity in male mice. Nature 2004; 427:411–2.
Merry BJ. Effect of dietary restriction on lifespan. Rev Clin Gerontol 1991; 1:203–213.
Jennings BJ, Ozanne SE, Hales CN. Nutrition, oxidative damage, telomere shortening and cellular senescence: Individual or connected agents of aging? Mol Gen Metab 2000; 71:32–42.
Kaufmann JA, Bickford PC, Taglialatela G. Oxidative-stress-dependent up-regulation of Bcl-2 expression in the central nervous system of aged Fischer-344 rats. J Neurochem 2001; 76:1099–1108.
Sohal RS, Agarwal S, Orr WC. Simultaneous overexpression of copper-containing and zinc-containing superoxide dismutase and catalase retards age-related oxidative damage and increases metabolic potential in Drosophila melanogaster. J Biol Chem 1995; 270:15671–15674.
Arivazhagan P, Juliet P, Panneerselvam C. Effect of DL-alpha lipoic acid on the status of lipid peroxidation and antioxidants in aged rats. Pharm Res 2000; 41:299–303.
Langley-Evans SC, Sculley DV, McMullen S. Increased oxidative injury in the liver of newborn rats exposed to intrauterine undernutrition is associated with reduced activity of superoxide dismutase. Ped Res 2003; 53:P103.
Langley-Evans SC, Wood S, Jackson AA. Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition. Ann Nutr Metab 1995; 39:28–35.
Langley-Evans SC, Phillips GJ, Jackson AA. Fetal exposure to a maternal low protein diet alters the susceptibility of the young adult rat to sulphur dioxide-induced lung injury. J Nutr 1997; 127:202–209.
Evans JR, Rauf A, Sayer AA et al. Age-related nuclear lens opacities are associated with reduced growth before 1 year of age. Inv.Opthal.Vis.Sci 1998; 39:1740–1744.
Sayer AA, Cooper C, Evans JR et al. Are rates of ageing determined in utero? Age and Ageing 1998; 27:579–583.
Dunn RL, Langley-Evans SC, Jackson AA et al. Hypertension in the mouse following intrauterine exposure to a low protein diet. Proc Nutr Soc 2001; 60:51A.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Eurekah.com and Springer Science+Business Media
About this chapter
Cite this chapter
Langley-Evans, S.C., Bellinger, L., Sculley, D., Langley-Evans, A., McMullen, S. (2006). Manipulation of the Maternal Diet in Rat Pregnancy. In: Wintour, E.M., Owens, J.A. (eds) Early Life Origins of Health and Disease. Advances in Experimental Medicine and Biology, vol 573. Springer, Boston, MA. https://doi.org/10.1007/0-387-32632-4_8
Download citation
DOI: https://doi.org/10.1007/0-387-32632-4_8
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-28715-7
Online ISBN: 978-0-387-32632-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)